Multi-Regional Clinical trials (MRCTs) can efficiently utilize limited resources to generate evidence to establish the safety and efficacy of innovative medicines but may be limited by potential heterogeneity among regions. The increased uncertainty and multiple layers of regulatory requirements have been challenges in using the framework of traditional models for clinical trials design and analysis. Recent literature has clarified this new landscape of multi regional clinical trials and provided direction to meet the new challenges. In this presentation, we will review some of these developments and provide our thoughts on possible gaps as well as potential solutions, including an optimal adaptive design to address certain gaps.